12.16 NEONATAL SEIZURES

TABLE 12.51: Causes of neonatal seizures with age of onset

Seizure is a common neonatal emergency, seen in ~0.5% of term and ~2.0% of preterm newborns. Apart from sudden death due to choking or aspiration, seizures may also lead to persistent hypoxic brain damage and long-term sequelae.

Clinical types: Neonatal seizures often present diffe­rently than in older children and adults with atypical manifestations, e.g.

• Subtle seizures, either with minimal motor activity involving eyes (vacant stare, upward gaze), face (chewing, tongue thrusting, lip smacking), or limbs (paddling, cycling, boxing); or sudden autonomic disturbances, e.g. apnea, tachycardia/bradycardia, etc.

• Clonic seizures with associated EEG abnormality, which carry best prognosis.

• Tonic seizures or decerebrate posture, usually without EEG changes.

• Myoclonic seizures with jerky movements of limbs or trunk, carry worst prognosis in terms of neuro- developmental outcome.

Neonatal seizures may also be classified as: (a) Electro- clinical seizures with clinical as well as EEG changes, (b) Clinical seizures without EEG changes, and (c) Electric seizures with abnormal EEG but no clinical presentation. Etiology: Metabolic seizures are most common in previously healthy newborn, while sick babies may convulse due to many causes, as follows:

• Hypoxia: HIE or intracranial hemorrhage.

• Infections: Meningitis, intrauterine infections, etc.

• Metabolic:

± Hypoglycemia

± Hypocalcemia with/without hypomagnesemia

± Pyridoxine dependency

± Dyselectrolytemia

± Inborn errors of metabolism (rare)

• CNS malformations: Microcephaly, hydrocephalus

• Kernicterus

• Vascular: Polycythemia, severe dehydration

• Iatrogenic: Narcotic withdrawal, aminophylline, acci­dental injection of local anaesthetics over fetal scalp during delivery—analgesia.

Diagnostic approach: Immediate control of seizures is more important than to identify its etiology. However, subsequent clinical evaluation and relevant investigations are necessary for etiological diagnosis and rational treatment, to prevent further attacks.

Diagnostic approach in these cases involves:

• Careful history regarding

± Age of onset (Table 12.51).

± Antenatal maternal infections or medications, etc.

± CNS anomalies or metabolic errors in family.

Day 1 seizures

• Birth asphyxia/hypoxic ischemic encephalopathy (HIE)

• Pyridoxine dependency

• Local anaesthetic injection in fetal scalp

Day 2-3 seizures

• All of the above, plus

• Metabolic: Hypoglycemia, hypocalcaemia, hypomagnesemia

• Birth injuries, e.g. Intracranial haemorrhage

• Developmental CNS malformations

• Tetanus neonatorum

• Narcotic withdrawal

Day 3-28 seizures

• All of the above except narcotic withdrawal, plus

• Infections, i.e. septicemia, meningitis

• Metabolic: Late-onset hypocalcemia

Pyridoxine dependency/deficiency Inborn errors of metabolism

• Benign familial neonatal seizures (5^th day fits)

• Others: Kernicterus

± Birth asphyxia, risk factors of neonatal sepsis.

± Delayed feeding (hypoglycemia), etc.

• Clinical examination for signs of:

± Sepsis/meningitis, e.g. sick child, bulging AF, etc.

± Neural tube defects, abnormal head size

± Intrauterine infections, e.g. low birth weight, hepatosplenomegaly, etc.

± Apparently well child (metabolic seizures).

• Laboratory investigations, including:

Step I. Base-line investigations

± Sepsis screen: Blood counts, CRP, etc.

± Metabolic screen: B. Sugar, S. Ca⁺⁺, Mg⁺⁺

± CSF examination including bacteriology ± Cranial USG for malformations or bleeds

Step II. Second-line investigations

± Neuroimaging: CT/MRI, EEG

± Serological (TORCH) screening

Step III. Select cases with unexplained seizures

± Screening tests for inborn errors of metabolism, e.g.

Differential diagnosis: Apart from etiological diffe­rentiation, neonatal seizures should also be differentiated from seizure mimics, e.g. jitteriness and being neonatal myoclonus.

Jitteriness is common in normal newborns during first 48 hours, characterized by fast, symmetrical and rhythmic movement of limbs without gaze abnormality, which can be easily stimulated by just touching the baby and can be rapidly abolished by mild restrain or passive flexion of limbs. Persistent and severe jitteriness may be a sign of: (a) cerebral hypoxia, (b) metabolic problems e.g. hypoglycemia, hypocalcemia, etc., (c) narcotic withdrawal, and (d) congenital thyrotoxicosis.

Benign myoclonus is sudden jerky movement of limbs in a newborn while asleep, which disappear on waking. Baby is otherwise normal and myoclonus subsides by 2-3 months without any treatment, with long term adverse outcome.

Management: All neonatal seizures need emergency hospitalization and the first priority lies in immediate control of seizures, irrespective of cause. Important steps in management include:

Step I. Ensure airway patency and adequate ventilation by cautious low-pressure suction, proper positioning (lateral/prone) to prevent aspiration and oxygen supplementation.

Step II. Establish an IV line for anticonvulsants, drugs and fluid-electrolyte correction. An IV anticonvulsant (as in step V) may be given at this stage, if seizures are life-threatening and unlikely to be metabolic.

Step III. Collect blood samples for metabolic screen, i.e. B. sugar, calcium and magnesium, as well as quick clinical evaluation.

Step IV. Empirical correction for common metabolic causes, specially in apparently healthy and term babies. This step involves step-wise correction of problems, as follows:

• IV Dextrose 10%, 2 ml/kg as bolus, followed by continuous infusion (6-8 mg/kg/min). If seizures are not controlled, then-

• IV Calcium gluconate 10%, 2 ml/kg (1:1 dilution in distilled water), slowly over 5-10 minutes with cardiac monitoring for bradycardia.

• IM Magnesium sulphate 50%, 0.2 ml/kg as bolus. If seizure are not yet controlled, then-

Step V. Specific anticonvulsant therapy should begin as early as possible, if metabolic cause is unlikely or no response to metabolic corrections (Step IV). Various anticonvulsants are used in step-wise manner with monitoring of response, as follows:

• IV Phenobarbitone 20 mg/kg, slowly over 20 minutes. Doses may repeated as 5-10 mg/kg twice after every 30 minutes (Total 40 mg/kg) in non-responders. Still, if seizures continue.

• IV Phenytoin 20 mg/kg, diluted in distilled water, slowly (lt;1 mg/kg/min) over 10-15 minutes IV or preferably IV Levetiracetam 50 mg/kg over 20 minutes. Fosphenytoin is preferred to Phenytoin in equivalent doses, if available. Still, if seizures continue.

• IV Midazolam (0.15 mg/kg as bolus followed by continuous infusion as 0.5-1 pg/kg for the ease of dosage titration. However, considering side-effects, e.g. sedation, benzodiazepines should not be used for long-term control. IV Lidocaine 2 mg/kg bolus followed by 6 mg/kg/hour may also be used to control refractory seizures, titrated down gradually

IV Pyridoxine 50-100 mg slowly under EEG monitoring may be tried in some refractory cases with dramatic response in cases of pyridoxine deficiency/ dependency seizures, which are common in newborns whose mothers have received high-dose pyridoxine therapy for hyperemesis gravidarum.

Step VI. Maintenance anticonvulsant therapy with Phenobarbitone (3-6 mg/kg/day q12h) or Phenytoin (4-8 mg/kg/day q12h) or Levetiracetam 40 mg/kg/ day q12h for 6-8 weeks is necessary in all non-metabolic seizures, the choice depending on the response in bolus therapy. Maintenance therapy should be started after 24 hours of last bolus dose. Unlike adults, prolonged anticonvulsant therapy is not required in most newborns due to little risk of recurrence in neonatal seizures and significant side effects on growth and development.

Specific therapy is needed for primary disease, e.g. meningitis, narcotic withdrawal, etc. apart from anticonvulsants.

Outcome of neonatal seizures depends on primary cause, though ~ 10-20% of untreated convulsing infants may die due to asphyxia and choking. Risk of long-term neurological deficit depends on the primary cause, though high-risk factors include—(a) onset of seizures on first day of life, (b) persistence beyond 48 hours despite anticonvulsant therapy and (c) myoclonic seizures. Metabolic seizures have best prognosis with very rare long­term neurological damage.

12.17